COPD大鼠模型海马组织代谢研究

Study of hippocampal metabolism in rats with chronic obstructive pulmonary disease

目的:探讨慢性阻塞性肺疾病(COPD)并发慢性脑损害的可能分子机制。方法:将24只大鼠随机分为正常对照组、单纯脂多糖组、单纯吸烟组、COPD模型组。采用被动吸烟联合气管内注射脂多糖方法建立COPD大鼠模型,在活体状态下进行高磁场Micro-MRI成像及双侧海马波谱采集,分析大鼠双侧海马氮-乙酰天门冬氨酸复合物(NAA)/肌酸(Cr)、胆碱复合物(Cho)/Cr之值的变化。结果:与正常对照组相比,COPD模型组双侧海马Cho/Cr值显著降低(P<0.05);单纯吸烟组、单纯脂多糖组左侧海马Cho/Cr值也较正常对照组明显低(P<0.05),右侧海马Cho/Cr值无明显差异(P>0.05)。单纯吸烟组、单纯脂多糖组、COPD模型3组间双侧海马Cho/Cr值无明显差异(P>0.05);各组间双侧海马NAA/Cr值无明显差异(P>0.05);各组内左右两侧NAA/Cr、Cho/Cr值无明显差异(P>0.05)。结论:COPD大鼠模型双侧海马Cho/Cr值明显降低,海马组织代谢异常可能是COPD并发慢性脑损害早期病理基础之一。

Objective: To explore the possible molecular mechanisms of chronic obstructive pulmonary disease(COPD) with chronic brain damage.Methods: 24 rats were randomly divided to control-group,lipopolysaccharide(LPS)-group,smoking-group,COPD model group.Rats with COPD(model group) was established by passive smoking and intratracheal instillation of LPS,and underwent brain micro-magnetic resonance imaging(MRI) and bilateral hippocampal proton magnetic resonance spectroscopy in vivo.A neurochemical profile consisting of metabolite concentrations,N-acetylaspartate(NAA)/creatine(Cr) and choline(Cho)/Cr metabolite ratios in the hippocampus were evaluated and analyzed.Results: Compared with control-group,the Cho/Cr ratios of bilateral hippocampus in COPD model group were significantly reduced(P<0.05).The Cho/Cr ratios of left hippocampus in LPS-group and smoking-group were significantly lower than control-group(P<0.05),but not in right hippocampus(P>0.05).There were no significant difference in Cho /Cr ratios of bilateral hippocampus among LPS-group,smoking-group and COPD model group(P>0.05).There was no groups different in NAA/Cr ratios of bilateral hippocampus among four groups(P>0.05).There was no significant difference in Cho/Cr and NAA/Cr ratios of bilateral hippocampus in every group(P>0.05).Conclusion: Cho/Cr of bilateral hippocampus in COPD model group is significantly reduced,suggesting that abnormal hippocampal neurochemistry may be an earlier pathology of COPD with chronic brain damage.